Mean Lesion Area Research Articles

Intravitreal Ranibizumab for Pigment Epithelium Detachment With Subfoveal Occult Choroidal Neovascularization: A Prospective 24-Month Case Series

To assess the effects of intravitreal ranibizumab injection in patients affected by pigment epithelial detachment associated with occult subfoveal choroidal neovascularization. Prospective, interventional case series. Forty eyes of 40 patients were considered for the purpose of the study. Consecutive patients were recruited for a 24-month study. All patients underwent a complete ophthalmic examination, including best-corrected visual acuity on Early Treatment Diabetic Retinopathy Study (ETDRS) charts. After a 3-monthly loading phase, further intravitreal ranibizumab injections were administered on the basis of detection of any type of fluid on optical coherence tomography. Changes in mean best-corrected visual acuity at 12 and 24months and the proportion of eyes losing fewer than 15 letters (corresponding to 3 ETDRS lines) from baseline visual acuity. Changes in central macular thickness on optical coherence tomography and variation in mean area of the entire lesion. Forty patients were included. Mean best-corrected visual acuity decreased from 20/66 (58 ETDRS letters) to 20/83 (53 letters) at 12months and 20/112 (489 ETDRS letters) at 24months (P= .003). Eighty percent and 67.5% of eyes lost fewer than 3 lines at 12 and 24months, respectively. Mean central macular thickness passed from 545μm to 428μm at 12months and 426μm at 24months. Mean lesion area changed from 6826μm(2) to 6312μm(2) at 12months and 6010μm(2) at 24months. The treatment of pigment epithelial detachment associated with occult subfoveal choroidal neovascularization with intravitreal ranibizumab injection after a 3-monthly loading phase and pro re nata strategy can lead to partial results over a 24-month follow-up. Further investigations are warranted to establish the best therapeutic approach to this disease.

Radiofrequency ablation in experimental bone metastases using a controlled and navigated ablation device

BackgroundRadiofrequency ablation is a minimal invasive therapy in the treatment of bone metastases. In this study we present a new ablation system enabling an ablation in multiple directions and with an adaptable size and shape. Material and methodsVX-2 tumor was used for the induction of experimental bone metastases in the femur of six New Zealand white rabbits. X-ray imaging as well as CT and MRI scans before and after treatment was carried out. After detecting bone tumor, radiofrequency ablation was performed. The ablation instrument contained a 10g bipolar, articulated extendable electrode and a proprietary generator with an impedance controlled algorithm. All bones and the soft tissue were examined histologically. ResultsAll animals developed local bone tumor. Mean duration until first osteolytic lesions on CT-scans was 48±14 days. The mean lesion area was 26mm2. No systemic tumor spread was seen. 6 radiofrequency procedures were carried out with a mean application time of 6min±2:30 and an average temperature in the region of effect of 55°C±4. MRI imaging demonstrated an ablation zone of 23±6mm around the electrode. Histopathology showed an extensive heat necrosis with no remaining tumor cells in the ablation area. ConclusionRadiofrequency ablation is a quickly developing treatment option on the field of minimal invasive bone tumor therapy. The electrode enables an ablation adapted to size and shape of the metastases. Further clinical studies are necessary to test and enhance this radiofrequency system.

Propranolol Reduces Infantile Hemangioma Volume and Vessel Density

To evaluate changes in infantile hemangioma tissue before and after propranolol therapy, using gray-scale and color Doppler ultrasound imaging. Case series with chart review. Tertiary pediatric hospital. Medical records and image studies of head and neck infantile hemangioma patients treated with propranolol, identified in a quality improvement database, were reviewed. Patients with imaging before and at least 4 weeks following the initiation of treatment were included. Data collected included sex, age, location, and concurrent treatment. Student t tests were used to evaluate change in cutaneous lesion area, volume, and vessel density. Logistic regression was used to compare lesion area, volume, and vessel density. Of the 177 patients identified, 19 met inclusion criteria. Fourteen of 19 were female, and 5 of 19 were older than 1 year. Mean lesion area change with treatment was 13.0 cm(2) (range, -2.8 to 28.9 cm(2), P = .05). Measured volume change was a mean of 10.3 cm(3) (range, 1.5-19.2 cm(3), P = .01). Mean vessel density change was 4.4 vessels per cm(2) (range, 2.5-6.3 vessels per cm(2), P < .01). Treatment decreased clinically determined hemangioma area proportionately less than gray-scale and color Doppler ultrasound measured lesion volume. Gray-scale and color Doppler ultrasound measured treatment response did not differ with sex, lesion location, or age at propranolol initiation. Gray-scale and color Doppler ultrasound imaging of propranolol-treated infantile hemangiomas detected a significant reduction in lesion volume and vessel density. Patient age at propranolol treatment and concomitant corticosteroid use did not affect lesion volume change.

Improved Radiological Localization of Spinal Cord Lesions in Multiple Sclerosis (P03.060)

Objective: To classify spinal cord lesions in multiple sclerosis (MS) based on white matter (WM) columns, and grey matter (GM) and WM involvement using magnetic resonance imaging (MRI). Background The localization of spinal cord lesions has not been well documented on MRI, although morphology and distribution of plaques have been characterized in post-mortem studies. Design/Methods: MRI was performed on the cervical cord in 16 MS patients (10 female, mean age 44.8) (8 relapsing remitting (RR) MS, 7 secondary progressive (SP) MS, 1 clinically isolated syndrome (CIS)). Axial phase sensitive inversion recovery (PSIR) and gradient-echo sequences were acquired. Two readers reviewed both images simultaneously and reached a consensus about classification of lesions by location: anterior (AC), lateral (LC) or posterior columns (PC). A sub-classification of lesions in mixed WM/GM and those involving WM only was also performed. Lesions were outlined manually on PSIR images and compared with mean cord area. Results: 51 lesions were identified, 24 in RRMS, 22 in SPMS, 5 in CIS. Three lesions were seen in AC (5.8%), 18 in PC (35.3%) and 30 in LC (58.9%). 33% of lesions involved WM alone and 67% involved both GM and WM; no pure GM lesions were identified. Mean lesion area in AC was 4.3mm2, LC 8.5mm2, PC 11.3mm2, with lesions in each column covering 6.1%, 12% and 16.1% of mean cord area respectively, mean lesion length in AC 18.3mm, LC 17.6mm and PC 24.8mm. Conclusions: Most lesions seen involved GM and WM, and were in the PC and LC, in agreement with post-mortem studies. However, no pure GM lesions were seen, suggesting technical limitations or a difference in patient characteristics from post-mortem studies. MRI may permit classification of spinal cord lesion location, area and length, which maybe correlated in future with disability to provide new insights into their functional effects. Supported by: MS Society. Disclosure: Dr. Kearney has nothing to disclose. Dr. Miszkiel has received research support from Biogen Idec and GlaxoSmithKline, Inc. Dr. Yiannakas has nothing to disclose. Dr. Ciccarelli has nothing to disclose. Dr. Miller has received personal compensation for activities with UCL Institute of Neurology, Biogen Idec, GlaxoSmithKline, and Bayer Schering Pharma. Dr. Miller has received personal compensation in an editorial capacity for Journal of Neurology. Dr. Miller has received research support from GlaxoSmithKline, Biogen Idec, and Novartis.

Su176 Ulcerogenic Effects of Plain and Enteric-Coated Aspirin on the Gastrointestinal Mucosa in Cats

BACKGROUND/AIM: Recently, low-dose aspirin (ASA) has been widely used as the firstchoice drug for the prophylaxis and treatment of thrombosis. Enteric-coated (EC) ASA has been used to limit gastric lesions as a side effect, but even low doses of EC ASA often cause mucosal damage in the small intestine in humans. However, there are few studies on the ulcerogenic effect of ASA on the small intestine in experimental animals. We examined the ulcerogenic effects of plain and EC ASA on the gastrointestinal (GI) mucosa in cats: i.e., 1) the effect of feeding (fasted vs fed) on ASA-induced GI lesions; 2) the effects of cimetidine and misoprostol on ASA-induced GI lesions; and 3) the ulcerogenic effect of EC ASA on the GI mucosa. METHODS: Adult cats were used (4 to 6 animals per group). In the fed group, either plain ASA (20 mg/kg) or 1 EC ASA tablet (containing 100 mg ASA) was administered p.o. once daily after the morning meal for 3 days, whereas in the fasted group, ASA was given in the morning after an overnight fast. The animals were sacrificed 24 h after the final ASA dose and mucosal lesions in the GI tract were examined. Both cimetidine and misoprostol were administered p.o. 30 min before the morning meal. RESULTS: (1) In the fasted condition, ASA caused lesions in the corpus, antrum, duodenum and small intestine; the mean lesion area (MLA) was 0.25±0.1 cm2, 0.04±0.01 cm2, 0.24±0.1 cm2 and 0.11±0.05 cm2, respectively. When ASA was given after feeding, the duodenal lesions were markedly increased; the MLA was 0.75±0.31 cm2 (P<0.05 vs. fasted). (2) Both cimetidine (20 mg/kg, p.o.) and misoprostol (3 μg/kg, p.o.) markedly inhibited lesion formation in the stomach, but they did not affect duodenal lesions. Furthermore, cimetidine significantly (P<0.01) increased the area of lesions in the small intestine; the MLAs were 0.93±0.14 cm2 (cimetidine) and 0.13±0.05 cm2 (vehicle group). (3) EC ASA tablet (18.5-29.4 mg/kg) given orally once a day for 3 or 7 days did not cause any visible lesions in the stomach, but lesions were evident both in the duodenum and small intestine. The area of lesions increased with the duration of treatment; the MLAs following 7-day treatment were 0.98±0.13 cm2 (duodenum) and 1.58±0.82 cm2 (small intestine). CONCLUSIONS: 1) Adverse effects of ASA on the GI mucosa seemed to be decreased when ASA was given in the fasted condition. 2) ASA-induced duodenal lesions are resistant to cimetidine and misoprostol, suggesting that ASA caused the lesions by directly injuring the mucosa. 3) Histamine H2-receptor antagonists may aggravate small intestinal lesions caused by ASA. 4) Adverse effects of ASA on the stomach were markedly improved with EC ASA, but this treatment still caused lesions in the duodenum and small intestine, indicating that additional research is necessary to determine how to further reduce the toxicity of EC ASA.

Osteochondral transplantation using autografts from the upper tibio-fibular joint for the treatment of knee cartilage lesions

Treatment of large cartilage lesions of the knee in weight-bearing areas is still a controversy and challenging topic. Autologous osteochondral mosaicplasty has proven to be a valid option for treatment but donor site morbidity with most frequently used autografts remains a source of concern. This study aims to assess clinical results and safety profile of autologous osteochondral graft from the upper tibio-fibular joint applied to reconstruct symptomatic osteochondral lesions of the knee. Thirty-one patients (22 men and 9 women) with grade 4 cartilage lesions in the knee were operated by mosaicplasty technique using autologous osteochondral graft from the upper tibio-fibular joint, between 1998 and 2006. Clinical assessment included visual analog scale (VAS) for pain and Lysholm score. All patients were evaluated by MRI pre- and post-operatively regarding joint congruency as good, fair (inferior to 1 mm incongruence), and poor (incongruence higher than 1 mm registered in any frame). Donor zone status was evaluated according to specific protocol considering upper tibio-fibular joint instability, pain, neurological complications, lateral collateral ligament insufficiency, or ankle complaints. Mean age at surgery was 30.1 years (SD 12.2). In respect to lesion sites, 22 were located in weight-bearing area of medial femoral condyle, 7 in lateral femoral condyle, 1 in trochlea, and 1 in patella. Mean follow-up was 110.1 months (SD 23.2). Mean area of lesion was 3.3 cm2 (SD 1.7), and a variable number of cylinders were used, mean 2.5 (SD 1.3). Mean VAS score improved from 47.1 (SD 10.1) to 20.0 (SD 11.5); p = 0.00. Similarly, mean Lysholm score increased from 45.7 (SD 4.5) to 85.3 (SD 7.0); p = 0.00. The level of patient satisfaction was evaluated, and 28 patients declared to be satisfied/very satisfied and would do surgery again, while 3 declared as unsatisfied with the procedure and would not submit to surgery again. These three patients had lower clinical scores and kept complaints related to the original problem but unrelated to donor zone. MRI score significantly improved at 18-24 months comparing with pre-operative (p = 0.004). No radiographic or clinical complications related to donor zone with implication in activity were registered. This work corroborates that mosaicplasty technique using autologous osteochondral graft from the upper tibio-fibular joint is effective to treat osteochondral defects in the knee joint. No relevant complications related to donor zone were registered. Case series, Level IV.

A prospective clinical study of polycarboxylate cement in periapical surgery

Objective: To evaluate the clinical efficacy of polycarboxylate cement as retrograde filling material. Design: A prospective clinical study was made of 25 patients subjected to periapical surgery with ultrasound and magnifying loupes, in which polycarboxylate cement was used as retrograde filling material. Measurements were made of the area and diameter of the lesions pre- and postoperatively, and 6 and 12 months after the operation. The apical resection and retrograde filling areas were also measured, and the prognosis following surgery was recorded. Results: A total of 23 patients with 31 apicoectomized teeth were studied (2 patients being lost to follow-up). The mean area of the periapical lesions before surgery was 52.25 mm2, with a mean major diameter of 6.1 mm and a mean lesser diameter of 4.8 mm. The success rate after 12 months was 54.7%, according to the criteria of Von Arx and Kurt. The prognosis was poorer in females, in larger lesions, and in cases with larger retrograde filling areas. Conclusions: Polycarboxylate cement offers good results, with important bone regeneration after periapical surgery. Key words: Periapical surgery, endodontic treatment, polycarboxylate cement.

The Anti-Thrombotic Enzyme ADAMTS13 Reduces Inflammation and the Development of Atherosclerosis In Mice

Abstract 367 Background and objective:ADAMTS13 (A Disintegrin-like And Metalloprotease with Thrombospondin type I repeats-13) plays a pivotal role in preventing spontaneous thrombosis in the microvasculature by cleaving hyperactive ultra large von Willebrand factor (ULVWF) multimers into smaller, less active multimers. Severe deficiency of ADAMTS13 in humans causes thrombotic thrombocytopenic purpura (TTP) and numerous epidemiological studies have demonstrated associations between decreased ADAMTS13 activity and adverse disease outcome in patients with systemic inflammation. It remains unknown, however, whether reduced ADAMTS13 activity plays a direct pathogenic role in inflammatory diseases or rather simply serves as an inflammation-associated marker. We hypothesized that deficiency of ADAMTS13 enhances inflammation and accelerates the development of early atherosclerotic plaques. Results:Using intravital fluorescence microscopy, we show that the number of adherent leukocytes (adherent for > 60 s) was increased approximately four-fold at the carotid sinus, a lesion prone site, of Adamts13−/−/ApoE−/− mice (Mean ± SEM = 37 ± 6) as compared to ApoE−/− mice (Mean ± SEM = 9 ± 4, P <0.01) fed a high-fat Western diet. Interestingly, intravital microscopy showed that 100% (10/10) of the Adamts13−/−/ApoE−/− mice had plaque that occluded the carotid sinus by approximately 70–80%, whereas only 20% (2/10) of the ApoE−/− mice had plaque at the carotid sinus, and the plaques were smaller in size than those in Adamts13−/−/ApoE−/− mice (P=0.0003). Next, we determined the effects of ADAMTS13 deficiency on atherosclerotic plaque formation in the aorta and aortic sinus. We compared the extent of atherosclerosis in whole aortae stained with Oil Red O and en face lesion area measured by morphometry. Both Adamts13−/−/ApoE−/− male and female mice demonstrated significantly larger lesions in the descending aorta (P<0.01), arch of the aorta (P<0.001), and total aorta (P<0.0001) compared to ApoE−/− mice fed a high-fat Western diet. Next, we quantified the corss-sectional area of lesions in the aortic sinus using the VerHoeffs/Van Gieson method. We observed a two-fold increase in the mean lesion area in the aortic sinus of both male and female Adamts13−/−/ApoE−/− mice (P<0.01) compared to ApoE−/− mice. Macrophage content (% of total lesion area), as quantitated by immunohistochemistry, was significantly elevated in the aortic root lesions of Adamts13−/−/ApoE−/− mice compared to ApoE−/− mice, suggesting that exacerbated atherosclerosis was due to increased inflammation. Adamts13−/−/ApoE−/− mice fed a normal chow diet also demonstrated accelerated atherosclerotic plaque formation compared to ApoE−/− mice. Total cholesterol and triglyceride levels were similar in Adamts13−/−/ApoE−/− and ApoE−/− mice fed a high-fat Western diet or normal chow diet. Conclusions:These findings unravel a new functional role for the anti-thrombotic enzyme ADAMTS13 in reducing excessive inflammation and plaque formation during atherosclerosis. Disclosures:Lentz:Celgene: Ownership interest; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

First Report of Iprodione Resistance in Botrytis cinerea on Blackberry from South Carolina.

Botrytis cinerea Pers.:Fr., is a necrotrophic fungus with a broad host range that causes gray mold on hundreds of plant species (2). Control of gray mold mainly depends on fungicides, including the dicarboxamide iprodione. Thirty-nine diseased blackberry fruit were collected from four orchards in South Carolina and the sensitivity of single-spore isolates to iprodione was examined by Spiral Plater assays (1) on potato dextrose agar (PDA). Briefly, a 5.3 cm long paper strip containing mycelia was placed along the concentration gradient of the PDA and 50% inhibition (EC50 value) was calculated after 2 days of incubation with the Spiral Gradient Endpoint (SGE) software (Spiral Biotech, Norwood, MA). Each isolate was tested in duplicates. Sensitivity ranged from 0.043 to 2.596 μg/ml, with a maximum resistance factor of 60.4. Isolates with EC50 values greater than 2 μg/ml were found in two orchards. Those isolates represented 40 and 7.1% of the total isolates from each orchard. Two isolates with high (EC50 value of 2.596 μg/ml) and low (EC50 value of 0.062 μg/ml) values were chosen to determine the efficacy of iprodione formulated product Rovral 4 Fl (Bayer CropSciences, Research Triangle Park, NC) on detached apple fruit. Fifteen apples were used for each isolate and experiment. Each fruit was wounded on the surface in three locations with a sterile syringe and inoculated with 15 μl of a spore suspension (106 conidia/ml) at the wounded sites. Rovral was applied at the recommended label rate either 24 h before (protective treatment) or 48 h after inoculation (curative treatment). The experiment was conducted three times. Blackberry fruit were not found suitable for this assay because of persistent contamination problems likely from latent infections of a symptomatic fruit. Disease incidence and lesion diameter were recorded 7 days after incubation. Disease incidence following inoculation of the sensitive and resistant isolates on non-fungicide-treated fruit was 100 and 86.7%, respectively. Disease incidence on fungicide-treated apples was 4.4% for the sensitive isolate and 75.6% for the resistant isolate with corresponding mean lesion areas of 0.36 mm and 9.37 mm, respectively. Both isolates were controlled effectively in protective treatments, however, indicating low levels of resistance. To our knowledge, this is the first report of iprodione resistance in B. cinerea from blackberry or any other field-grown crop in South Carolina. This finding adds to a study from 1999 (3) documenting resistance to the dicarboxamide fungicide vinclozolin in B. cinerea collected from ornamentals in South Carolinian greenhouses and suggests that resistance to iprodione needs to be considered in the design of gray mold control strategies in commercial blackberry orchards. No cross resistance between the phenylpyrrole fludioxonil and iprodione was found.

Safety and Tolerability of Combination Acyclovir 5% and Hydrocortisone 1% Cream in Adolescents with Recurrent Herpes Simplex Labialis

A Phase 3, open-label, multicenter study was conducted to assess the safety of the combination of 5% acyclovir and 1% hydrocortisone cream (AHC cream) in the treatment of recurrent herpes simplex labialis (HSL) in immunocompetent adolescents. Eligible subjects were aged 12 to 17 years and had a history of recurrent labial herpes with two or more episodes during the last 12 months. Subjects initiated treatment at the first signs or symptoms of a herpes recurrence-at the earliest prodromal phase and preferably before the presence of papules or vesicles. Subjects applied the cream topically five times per day for 5 days. Adverse events, categorization of recurrence (ulcerative or nonulcerative), and maximum lesion area (maximum area of an ulcerative lesion) were assessed. Of the 134 subjects analyzed for safety, 131 had data for categorization of recurrence at the post-treatment visit 3 ± 1 weeks after the last dose. Seventy-eight subjects (59.5%) had nonulcerative recurrences, and 53 (40.5%) had ulcerative recurrences. All 131 subjects reached the stage of normal skin, with no signs or symptoms, at the follow-up visit. The mean maximum lesion area in the 53 subjects with ulcerative herpes lesion was 39 mm(2). Five subjects reported five adverse events (secondary herpes labialis recurrences, n = 2; infectious rhinitis, n = 1; application site inflammation, n = 1; bronchial asthma, n = 1). All adverse events were of mild to moderate intensity. The results of this study demonstrate that the combination of AHC cream is well tolerated in the treatment of recurrent HSL in adolescents.

Açaí juice attenuates atherosclerosis in ApoE deficient mice through antioxidant and anti-inflammatory activities

ObjectiveAçaí fruit pulp has received much attention because of its high antioxidant capacity and potential anti-inflammatory effects. In this study, athero-protective effects of açaí juice were investigated in apolipoprotein E deficient (apoE−/−) mice. Methods and resultsApoE−/− mice were fed AIN-93G diet (CD) or CD formulated to contain 5% freeze-dried açaí juice powder (AJ) for 20 weeks. The mean lesion areas in the aorta for apoE−/− mice fed AJ were 58% less (P<0.001) compared to that for CD fed mice. HDL-cholesterol was higher in AJ fed mice. Biomarkers of lipid peroxidation, including F2-isoprostanes and isomers of hydroxyoctadecadienoic acids and hydroxyeicosatetraenoic acids were significantly lower in serum and in liver of AJ fed mice. Expression of the two antioxidant enzyme genes, Gpx3 and Gsr, were significantly up-regulated in the aorta from AJ fed mice. The activity of GPX, GSR and PON1 increased in serum and/or liver of mice fed AJ. In the second experiment, ApoE−/− mice were fed CD or AJ for 5 weeks. Serum levels, gene expression and protein levels of the two proinflammatory cytokines TNF-α and IL-6 in the resident macrophages with or without LPS stimulation were lower in mice fed AJ. SEAP reporter assay determined that AJ reduced NF-κB activation. ConclusionReducing lipid peroxidation through boosting antioxidant enzymes and inhibiting pro-inflammatory cytokine production are proposed as major underlying mechanisms for the athero-protective effects of the açaí juice tested in these experimental in vivo models.

Development of polypoidal lesions in age-related macular degeneration

To investigate the development of polypoidal lesions using indocyanine green angiography (IA) in eyes with typical age-related macular degeneration (AMD). We retrospectively reviewed the medical records of 47 consecutive patients (47 eyes) with typical AMD who had been followed up with IA for at least 2 years. At the initial visit, although all eyes showed classic and/or occult choroidal neovascularization (CNV) associated with AMD, no eyes showed polypoidal lesions by IA. However, during follow-up, 13 (27.7%) of the 47 eyes did show polypoidal lesions. All polypoidal lesions developed at the edge of persistent CNV or, more often, at the terminus of recently progressed CNV. Of 12 eyes with a final lesion area >8 disc area, 7 (58.3%) showed newly developed polypoidal lesions. In the eyes with these newly developed polypoidal lesions, the mean area of the vascular lesion had extended significantly from 10.50 ± 7.88 mm² to 20.87 ± 10.21 mm² during follow-up (P=0.0018). The current observation suggests that IA of active AMD sometimes reveals polypoidal lesions if there is progression of the CNV in the subretinal pigment epithelium space.

Acyclovir and hydrocortisone cream for the early treatment of recurrent cold sores

Acyclovir and hydrocortisone cream for the early treatment of recurrent cold sores Carrie A Sailer1, Spotswood L Spruance2, Christopher M Hull11Department of Dermatology, 2Department of Medicine, Division of Infectious Diseases, University of Utah, Salt Lake City, USAAbstract: Current antiviral therapies for herpes simplex labialis primarily reduce healing time. Since the host immune response also plays a role in both controlling recurrent infection as well as producing clinical symptoms, new studies are showing efficacy using topical corticosteroids. This review will evaluate the safety and efficacy of 5% acyclovir&ndash;1% hydrocortisone cream (Xerese&trade;[US], Xerclear&reg;[Europe]) for treatment of patients with herpes simplex labialis. A large, randomized, double-blind, placebo-controlled study recently demonstrated that treatment with 5% acyclovir&ndash;1% hydrocortisone cream significantly decreased the percentage of ulcerative lesions, reduced lesion healing time, and decreased mean lesion area compared with both topical acyclovir alone and vehicle.Keywords: herpes labialis, herpes simplex virus, HSV, acyclovir, hydrocortisone, ME-609, Xerese, Xerclear

Dietary Blueberries Attenuate Atherosclerosis in Apolipoprotein E-Deficient Mice by Upregulating Antioxidant Enzyme Expression1–4

Protective effects of blueberries (BB) against atherosclerosis and potential underlying mechanisms in reducing oxidative stress were examined in apoE-deficient (apoE− / −) mice. ApoE− / − mice were fed an AIN-93G diet (CD) or CD formulated to contain 1% freeze-dried whole BB for 20 wk. The mean lesion area for apoE− / − mice fed BB was reduced by 39% (P lt 0.001) in the aorta sinus and 58% (P lt 0.001) in the descending aorta compared with CD-fed mice. These atheroprotective effects were independent of the serum lipid profile or total antioxidant capacity (as measured by oxygen radical absorbance capacity). The concentration of a biomarker of lipid peroxidation, F2-isoprostane, was lower in liver of BB-fed mice (P lt 0.05). Genes analyzed by RT-PCR array showed that 4 major antioxidant enzymes in aorta [superoxide dismutase (SOD) 1, SOD2, glutathione reductase (GSR), and thioredoxin reductase 1] were upregulated in BB-fed mice. Enzyme activities of SOD and GSR were greater (P lt 0.05) in liver and/or serum of BB-fed mice than those of CD-fed mice. In addition, serum paraoxonase 1 activity in serum of BB-fed mice was also greater than that of CD-fed mice (P lt 0.05) at the end of the study. These results suggest a protective effectiveness of BB against atherosclerosis in this apoE− / − mouse model. The potential mechanisms may involve reduction in oxidative stress by both inhibition of lipid peroxidation and enhancement of antioxidant defense.

Tolerability and safety of conventional therapy combination with DeMarco formula for infected ischemic diabetic foot

Background A study has found that major amputations are necessary on 69% of ischemic diabetic foot patients treated with conventional therapy. An uncontrolled study of 31 patients showed that only 33% needed major amputation after treatment with conventional therapy plus De Marco Formula (DMF), a novel formulation of procaine and Polyvinylpyrrolidone. Objective To assess the tolerability and safety of the combination of conventional therapy and De Marco Formula for infected ischemic diabetic foot. Methods Adult patients, 10 male/24 female, were treated with the conventional therapy for diabetic foot plus DMF (0.15 ml/kg/day IM) during ten days and then twice a week until healing of the lesions or completion of a 52-day period. Required amputations, lesion areas, adverse events occurrence and clinical laboratory parameters (hemoglobin, blood cell counts, glycosilated hemoglobin, total proteins, creatinine, alanine transaminase and alkaline phosphatase) were determined during the treatment period. Results Two slight (5.88%) and one moderate (2.94%) adverse events (mainly cutaneous rash) were reported. The last one was reported on the 15th day of treatment and DMF dosing was discontinued by patient’s request. Clinical laboratory mean values remained within normal ranges during treatment except for blood leukocyte counts that pathologically elevated at baseline and decreased to normality by treatment end. This study has found that 18.08% of patients ( N = 6) needed a lower limb amputation with the combined treatments. The standard reported rate in Cuba is 25–29%. Furthermore, a progressive reduction of the mean lesion area from 51.29 cm 2 at the beginning to 1.89 cm 2 at the end of the treatment ( p = 0.000001) was observed. Conclusion The treatment with De Marco Formula for 52 days as an adjuvant for the conventional therapy for infected ischemic diabetic foot was well tolerated and safe. These findings are consistent with those of a randomized prospective controlled study performed later.

Heparin inhibits the production of matrix metalloproteinase-2 and improves atherosclerosis in LDL receptor-deficient mice

This study aimed to find the effects of heparin on atherosclerosis and the production of matrix metalloproteinase (MMP)-2 in low-density lipoprotein receptor-deficient (LDLr(-/-)) mice. Sixteen 7-week-old LDLr(-/-) mice were randomized to receive sterile water or heparin. The levels of total cholesterol, high-density lipoprotein cholesterol, triglyceride and homocysteine were measured. Mean lesions area was calculated as the total atherosclerotic lesions area and expressed as a percentage of total luminal surface area. The lesions area was measured blindly by the same person using computer-assisted image analysis. The expression and localization of the MMP-2 was examined by immunohistochemistry. All mice exhibited atherosclerotic lesions in the aortic sinus and aortic surface. Total cholesterol was decreased, while high-density lipoprotein cholesterol was increased in heparin compared with that in control group (P=0.001 and 0.002). Triglyceride was not significantly different between the two groups (P=0.92). The amount of atherosclerotic lesions in the aortic surface was 40.5% lower in heparin group than that in the control group (P<0.001). The mean area of atherosclerotic lesions in the aortic sinus was also less in the heparin group than that in the control group. Coincidently, the expression of MMP-2 in the atherosclerotic lesions in the heparin group was 49.3% lower than that in the control group (P<0.001). Heparin can inhibit the production of MMP-2 in the atherosclerotic lesions and improve the atherosclerotic lesions in LDLr(-/-) mice.

Effects of combination therapy with verteporfin photodynamic therapy and ranibizumab in patients with age-related macular degeneration

This open-label, prospective, small-scale study investigated the benefits of same-day verteporfin and intravitreal ranibizumab in patients with predominantly classic, minimally classic or occult subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration. Patients received verteporfin at baseline and at month 3, if leakage persisted. Ranibizumab (0.5 mg) was given at baseline and months 1, 2 and 3, and thereafter at monthly intervals if required. Same-day ranibizumab was given ≥ 1 hr after verteporfin. Fifteen patients [11 male, four female; mean age 75.5 years (range 54-94 years)] were treated. At day 360, mean visual acuity (VA) had improved by 10.9 letters. An increase of ≥ 15 and ≥ 30 letters (i.e. ≥ 3 and ≥ 6 lines) was observed in seven (47%) patients and one patient (7%), respectively. Mean central retinal thickness (CRT) decreased by 85 μm. At days 7, 14 and 30, CNV perfusion was absent in 14/15 patients. Mean lesion area had reduced from baseline by 23.1% at day 120, 25.5% at day 180 and 23.6% at day 360. There were no visual safety concerns and intraocular pressures remained normal. Only two serious adverse events were recorded over the 12-month period, and neither was considered to be related to treatment. Same-day verteporfin plus ranibizumab improved VA, reduced CRT, prevented CNV perfusion and reduced lesion area safely over 12 months. Further investigation is warranted to confirm whether this combination improves long-term vision and reduces the need for retreatment.

Effects of blueberries in prevention of atherosclerosis in ApoE knockout mice

ApoE knockout (ApoE−/−) mice were fed AIN‐93G diet (CD) or CD formulated to contain 1% freeze‐dried whole wild blueberries (CD1% BB). Mice were sacrificed after 20 weeks on the specified diet. Atherosclerotic lesions in aortic sinus were determined by staining cryosections (10 μm) with Oil Red O. The mean lesion area for ApoE−/− mice fed the CD1% BB was reduced by 39% (P &lt;0.01) compared to CD fed animals. Serum LDL‐cholesterol and triglyceride levels were slightly lower in ApoE−/− mice fed CD1%BB (NS) compared to CD fed animals. Serum paraoxonase 1 activities in serum of CD1%BB animals were higher than that in CD animals (P&lt;0.05). Superoxide dismutase activities in both serum and liver were found to be increased (P&lt;0.05) in CD1%BB‐fed animals. Serum total antioxidant capacity measured by ORAC was not different between CD and CD1%BB fed animals, though a slight increase in CD1%BB‐fed animals was observed. These results indicated that anti‐atherogenic effects of BB are probably independent of changes in serum lipid profile. Furthermore, in addition to directly scavenging free radicals, BB in the diet altered antioxidant status by increasing antioxidant enzymes. (USDA‐CRIS‐6251‐5100002‐06S)

Susceptibility of Iberian trees to Phytophthora ramorum and P. cinnamomi

The capacity of Phytophthora ramorum to colonize the inner bark of 18 native and two exotic tree species from the Iberian Peninsula was tested. Living logs were wound‐inoculated in a growth chamber with three isolates belonging to the EU1 and two to the NA1 clonal lineages of P. ramorum. Most of the Quercus species ranked as highly susceptible in experiments carried out in summer, with mean lesion areas over 100 cm2 in Q. pubescens, Q. pyrenaica, Q. faginea and Q. suber and as large as 273 cm2 in Q. canariensis, ca. 40 days after inoculation. Quercus ilex ranked as moderately susceptible to P. ramorum, forming lesions up to 133 cm2 (average 17·2 cm2). Pinus halepensis and P. pinea were highly susceptible, exhibiting long, narrow lesions; but three other pine species, P. pinaster, P. nigra and P. sylvestris, were resistant to slightly susceptible. No significant difference in aggressiveness was found between the isolates of P. ramorum. In addition, there was evidence of genetic variation in susceptibility within host populations, and of significant seasonal variation in host susceptibility in some Quercus species. The results suggest a high risk of some Iberian oaks to P. ramorum, especially in forest ecosystems in southwestern Spain, where relict populations of Q. canariensis grow amongst susceptible understory species such as Rhododendron ponticum and Viburnum tinus. One isolate of P. cinnamomi used as positive control in all the inoculations was also highly aggressive to Iberian oaks and Eucalyptus dalrympleana.

A Phase II, Open‐Label Study of the Efficacy and Safety of Imiquimod in the Treatment of Superficial and Mixed Infantile Hemangioma

To explore the efficacy and safety of imiquimod 5% cream as a treatment for infantile hemangioma. Phase II, open-label, noncomparative study of imiquimod applied during 16 weeks, with posttherapy follow-up 16 weeks later (8 months total). Outpatient pediatric tertiary care referral center in Quebec, Canada. Healthy infants up to 8.8 months of age with previously untreated, nonulcerated, proliferative superficial or mixed infantile hemangioma, excluding periorbital, or perineal localization, > or =100 cm2 in size. Topical imiquimod applied three to seven times per week for 16 weeks to infantile hemangioma. Lesion area, volume, depth (Doppler ultrasound), and color (erythema), serum drug, and interferon-alpha levels. Sixteen infants (11 girls, 5 boys) with a mean age at entry of 4.1 months and mean lesion area of 32.89 cm2, and volume of 39.98 cm3 were enrolled. Two participants discontinued treatment early, one for an adverse event (crying upon application), the other because of the lack of compliance. Local skin reactions were consistent with those reported in adults. Two cases had a decrease and three had an increase in lesion parameters; otherwise no meaningful changes in lesion area, volume, or depth were observed. At the 4-month posttreatment visit, 11 of 14 subjects had improvement in erythema (marginal homogeneity test = 2.668, p = 0.008). Measured serum drug and interferon-alpha levels were low or undetectable. Treatment of infants with infantile hemangioma with imiquimod up to seven times per week for 16 weeks was generally well tolerated with low systemic exposure. Improvement was observed in hemangioma coloration, but not lesion size, suggesting effects were limited to the superficial component.